Acanthamoeba keratitis is a painful, vision-threatening corneal infection caused by pathogenic environmental amoebae. Acanthamoeba spp. are free-living opportunistic protozoa pathogens that are ubiquitous in many diverse environments including air, soil, freshwater, seawater, tap water, bottled water, swimming pools, sewage, and vegetables. Corneal infection with Acanthamoeba spp. was first described in humans during the mid-1970's. Since this time, dramatic increases in the number of human cases have been reported and Acanthamoeba keratitis is now widely recognized as an emerging ocular surface infection.
The frequency of Acanthamoeba keratitis is continuing to increase in many countries, including the United States, as a result of an expanding population of individuals at risk for infection, enhanced recognition of infection, improvements in diagnostic techniques, and sporadic outbreaks of infection associated with alterations of contact lens wear, contact lens handling, and water quality. The true incidence of Acanthamoeba keratitis is not currently known and varies widely among different geographical regions; however, recent estimates include 1 case per 30,000 hydrogel contact lens wearers per year in Europe, England, and Hong Kong; 1 case per 10,000 contact lens wearers per year in the United States; and 1 case per 4,200 outpatient visits to tertiary referral hospitals in Australia.
Acanthamoeba keratitis most commonly occurs in immunocompetent, healthy individuals and the most important and prevalent risk factors are contact lens wear, corneal trauma, and exposure to contaminated water or soil. Acanthamoeba trophozoites and cysts are capable of firmly adhering to soft contact lenses, a characteristic that explains the strong association between contact lens wear and infection. The clinical features of Acanthamoeba keratitis are diverse and non-specific. Corneal epithelial irregularities, epithelial ulcers, stromal infiltrates, stromal ulcers, radial keratoneuritis, and keratomalacia are common. These clinical features mimic infection with bacteria, viruses, and fungi; and amoebic keratitis is often initially misdiagnosed clinically. The diagnosis of Acanthamoeba keratitis is based upon demonstration of the organism or its nucleic acid with culture, cytology, histopathology, PCR, or in vivo corneal confocal microscopy.
Treatment of Acanthamoeba keratitis is lengthy and difficult, as few agents are effective at eliminating the cyst stage of Acanthamoeba within corneal tissues. Various therapeutic agents, including the diamidines, biguanides, imidazoles, and aminoglycosides have been reported with variable treatment results. Adverse ocular reactions attributable to the toxic properties of these compounds occur frequently. Treatment is often continued for a year or more and infection recurrences may develop after apparently successful medical therapy. Therapeutic keratoplasty has been used to manage acute complications associated with Acanthamoeba keratitis, but with generally poor results attributable to graft rejection and extension of Acanthamoeba infection into the graft. Therapeutic keratoplasty to resolve corneal scarring and astigmatism performed following a course of medical anti-amoebic therapy is associated with an improved surgical prognosis; however, exacerbation of ocular inflammation and graft infection still occur frequently.
The prognosis for Acanthamoeba keratitis is affected by severity of disease on presentation and the interval between the onset of symptoms and the start of appropriate therapy. Outcomes in the largest series of patients with Acanthamoeba keratitis reported that 11% of patients will require therapeutic keratoplasty, 6% require cataract surgery for complications associated with the infection or its therapy, and 2% require enucleation. Greater than 30% of patients completing treatment have 6/9 or poorer visual acuity, with 4% having only light perception or complete blindness.
The principal challenge for improving outcomes of patients with Acanthamoeba keratitis is the development of more effective drugs for the treatment and elimination of Acanthamoeba cysts within corneal tissues. Additionally, the pathogenesis of Acanthamoeba keratitis remains incompletely understood and the relative contribution of Acanthamoeba and host-derived factors in inducing tissue destruction is not clear. A major obstacle to improved understanding and treatment of Acanthamoeba keratitis is the lack of an appropriate animal model for comparative study. Acanthamoeba keratitis has been experimentally induced in pigs, rats, and Chinese hamsters; however, no spontaneous amoeba corneal infections have been identified in these animal species and the models have only been used on a limited basis since their publication. These animal models of Acanthamoeba keratitis develop ocular lesions that are clinically dissimilar from that of humans, require extensive host manipulation to induce infection, and possess ocular anatomy and physiology that is markedly different than humans. An improved animal model of Acanthamoeba keratitis would dramatically assist research efforts.
The suitability of an animal model of an ocular infectious disease is typically determined by considering four variables: 1) the animal's possession of anatomical and physiological characteristics consistent with the needs of the experiment and similar to the host being studied, 2) the presence of a naturally-occurring disease state in the species similar to the condition being studied, 3) cost and difficulty of acquiring and maintaining the animal species, and 4) availability of microbiologically defined animals for the infection of interest. The pig, rat, and hamster models of Acanthamoeba keratitis each fail to satisfy at least 2 of the criteria necessary for an optimal ocular infectious disease model. The pig, rat, and hamster models require extensive experimental host manipulation to establish Acanthamoeba infection and result in clinical ocular disease dissimilar to that observed in humans. The small globe size of rats and hamsters is difficult to examine in vivo and experimentally manipulate. Pigs are potentially dangerous to handle, expensive, and difficult to maintain.